The aims of this program are directed toward a major long-term goal: the establishment (through the use of restriction fragment length polymorphisms, abbreviated RFLPs) of a set of genetic markers which can be used to construct a true genetic map of the human genome. An example of a RFLP with a very high degree of polymorphism has recently been described (Wyman & White, Proc. Nat. Acad. Sci. USA 77:6754 [1980]); when used as probe, a plasmid (pAW101) reveals enough variation among individuals so that virtually any random mating will be informative about the inheritance of the locus. The specific aims of this research are four: 1) To examine the molecular basis of the high degree of DNA restriction fragment length polymorphism at the locus defined by the plasmid pAW101. It is hoped that his analysis will provide a rational means for finding rapidly other loci with very high polymorphism. 2) To screen, using libraries of hybrid lambda phage carrying human DNA, for loci showing high degrees of restriction fragment length polymorphism comparable to that found at the locus defined by pAW101. 3) To use somatic-cell hybrids to determine the chromosomal origin of cloned single-copy human DNA sequences. 4) To follow, in human families, the inheritance of restriction fragment length polymorphisms (RFLPs) and, if present, to detect linkage among RFLPs or between RFLPs and other inherited traits.